AST-to-Platelet Ratio Index as Potential Early-Warning Biomarker for Sepsis-Associated Liver Injury in Children: A Database Study

Jiaying Dou, Yiping Zhou, Yun Cui, Min Chen, Chunxia Wang, Yucai Zhang, Jiaying Dou, Yiping Zhou, Yun Cui, Min Chen, Chunxia Wang, Yucai Zhang

Abstract

Background: Sepsis-associated liver injury (SALI) is a risk factor of poor outcome in patients with sepsis. The early warning biomarkers for identifying SALI remain poorly defined. Aims: To identify the potential predictors of occurrence of SALI in pediatric patients with sepsis. Methods: We retrospectively analyzed the sepsis database based on the medical records of patients admitted to the pediatric intensive care unit (PICU) in Shanghai Children's Hospital from July 2014 to June 2018. Patients' demographics, co-morbidities and laboratory variables were collected. Univariate and multivariate logistic analysis were used to explore risk factors of SALI, and receiver operating characteristic (ROC) curve analysis was used to evaluate their predictive significances for SALI occurrence. Results: Of 1,645 eligible patients, 1,147 patients were included, and 105 cases had SALI. The indexes including AST-to-platelet ratio index (APRI), γ-GT and lactate dehydrogenase (LDH) were independent risk factors for SALI. Moreover, APRI was powerful to predict SALI in children (AUC: 0.889, 95% CI: 0.851-0.927) with a sensitivity of 84.6 % and a specificity of 84.3 % at the cutoff point of 0.340. APRI was superior to LDH and not inferior to γ-GT for predicting SALI. Conclusion: APRI is an independent risk factor of SALI occurrence, and elevated APRI within 24 h after PICU admission (>0.340) is a potential predictor for SALI in children.

Keywords: APRI; child; early-warning; liver injury; sepsis.

Figures

Figure 1
Figure 1
Flowchart of patients included in this study.
Figure 2
Figure 2
The values of APRI, MPV/PLT or PLT/WBC based on the first serological parameters within 24 h after PICU admission in pediatric patients with sepsis or sepsis-associated liver injury (SALI). (A) APRI, (B) MPV/PLT, and (C) PLT/WBC.
Figure 3
Figure 3
The ROC curves for APRI, LDH or γ-GT to predict the occurrence of sepsis-associated liver injury (SALI). (A) APRI, (B) LDH, and (C) γ-GT.

References

    1. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. . Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. (2017) 45:486–552. 10.1097/CCM.0000000000002255
    1. Yan J, Li S, Li S. The role of the liver in sepsis. Int Rev Immunol. (2014) 33:498–510. 10.3109/08830185.2014.889129
    1. Thomas H. Sepsis: bile acids promote inflammation in cholestasis-associated sepsis. Nat Rev Gastroenterol Hepatol. (2017) 14:324–5. 10.1038/nrgastro.2017.55
    1. Dhainaut JF, Marin N, Mignon A, Vinsonneau C. Hepatic response to sepsis: interaction between coagulation and inflammatory processes. Crit Care Med. (2001) 29:S42–7. 10.1097/00003246-200107001-00016
    1. Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. (2005) 6:2–8. 10.1097/01.PCC.0000149131.72248.E6
    1. Zagory JA, Dossa A, Golden J, Jensen AR, Goodhue CJ, Upperman JS, et al. . Re-evaluation of liver transaminase cutoff for CT after pediatric blunt abdominal trauma. Pediatr Surg Int. (2017) 33:311–6. 10.1007/s00383-016-4026-7
    1. Graham SM, Conrad Liles W. Platelets in sepsis: beyond hemostasis. Blood. (2016) 127:2947–9. 10.1182/blood-2016-03-706168
    1. Cato LD, Wearn CM, Bishop JRB, Stone MJ, Harrison P, Moiemen N. Platelet count: a predictor of sepsis and mortality in severe burns. Burns. (2018) 44:288–97. 10.1016/j.burns.2017.08.015
    1. Oh GH, Chung SP, Park YS, Hong JH, Lee HS, Chung HS, et al. . Mean platelet volume to platelet count ratio as a promising predictor of early mortality in severe sepsis. Shock. (2017) 47:323–30. 10.1097/SHK.0000000000000718
    1. Huang R, Wang J, Xia J, Zhang Z, Wu C. Platelet count and prediction of bleeding in patients with liver cirrhosis. Am J Gastroenterol. (2018) 113:1396–7. 10.1038/s41395-018-0152-2
    1. Iida H, Kaibori M, Matsui K, Ishizaki M, Kon M. Ratio of mean platelet volume to platelet count is a potential surrogate marker predicting liver cirrhosis. World J Hepatol. (2018) 10:82–7. 10.4254/wjh.v10.i1.82
    1. Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, et al. . Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. (2011) 53:726–36. 10.1002/hep.24105
    1. Peleg N, Issachar A, Sneh-Arbib O, Shlomai A. AST to Platelet Ratio Index and fibrosis 4 calculator scores for non-invasive assessment of hepatic fibrosis in patients with non-alcoholic fatty liver disease. Dig Liver Dis. (2017) 49:1133–8. 10.1016/j.dld.2017.05.002
    1. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. (2007) 71:1028–35. 10.1038/sj.ki.5002231
    1. El Shaer SS, Salaheldin TA, Saied NM, Abdelazim SM. In vivo ameliorative effect of cerium oxide nanoparticles in isoproterenol-induced cardiac toxicity. Exp Toxicol Pathol. (2017) 69:435–41. 10.1016/j.etp.2017.03.001
    1. Kobashi H, Toshimori J, Yamamoto K. Sepsis-associated liver injury: incidence, classification and the clinical significance. Hepatol Res. (2013) 43:255–66. 10.1111/j.1872-034X.2012.01069.x
    1. Nesseler N, Launey Y, Aninat C, Morel F, Malledant Y, Seguin P. Clinical review: the liver in sepsis. Crit Care. (2012) 16:235. 10.1186/cc11381
    1. Nesseler N, Launey Y, Aninat C, White J, Corlu A, Pieper K, et al. . Liver dysfunction is associated with long-term mortality in septic shock. Am J Respir Crit Care Med. (2016) 193:335–7. 10.1164/rccm.201508-1660LE
    1. Patel JJ, Taneja A, Niccum D, Kumar G, Jacobs E, Nanchal R. The association of serum bilirubin levels on the outcomes of severe sepsis. J Intensive Care Med. (2015) 30:23–9. 10.1177/0885066613488739
    1. Zaritsky AL, Nadkarni VM, Hickey RW, AL E. Pediatric Advanced Life Support Provider Manual. Dallas, TX: American Heart Association; (2002).
    1. Church RJ, Kullak-Ublick GA, Aubrecht J, Bonkovsky HL, Chalasani N, Fontana RJ, et al. . Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: an international collaborative effort. Hepatology. (2019) 69:760–73. 10.1002/hep.29802
    1. Sakurai K, Miyashita T, Okazaki M, Yamaguchi T, Ohbatake Y, Nakanuma S, et al. . Role for Neutrophil Extracellular Traps (NETs) and platelet aggregation in early sepsis-induced hepatic dysfunction. In vivo. (2017) 31:1051–8. 10.21873/invivo.11169
    1. Meyer J, Lejmi E, Fontana P, Morel P, Gonelle-Gispert C, Buhler L. A focus on the role of platelets in liver regeneration: do platelet-endothelial cell interactions initiate the regenerative process? J Hepatol. (2015) 63:1263–71. 10.1016/j.jhep.2015.07.002
    1. Deutschman CS, Cereda M, Ochroch EA, Raj NR. Sepsis-induced cholestasis, steatosis, hepatocellular injury, and impaired hepatocellular regeneration are enhanced in interleukin-6 -/- mice. Crit Care Med. (2006) 34:2613–20. 10.1097/01.CCM.0000240229.98275.07
    1. Vongbhavit K, Underwood MA. Predictive value of the aspartate aminotransferase to platelet ratio index for parenteral nutrition-associated cholestasis in premature infants with intestinal perforation. J Parenter Enteral Nutr. (2018) 42:797–804. 10.1177/0148607117722755
    1. Diaz JJ, Gura KM, Roda J, Perez-Atayde AR, Duggan C, Jaksic T, et al. Aspartate aminotransferase to platelet ratio index correlates with hepatic cirrhosis but not with fibrosis in pediatric patients with intestinal failure. J Pediatr Gastroenterol Nutr. (2013) 57:367–71. 10.1097/MPG.0b013e318299fdbd

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